The invention relates to a molecule for functionalizing the surface of an inert support and to the use in the preparation of a radionuclide of high purity in a generator. The invention relates in particular to a molecule for attaching a radioactive parent nuclide, in particular germanium-68, to a support.
Radionuclides, in particular positron emitters, are used in positron emission tomography (PET). In the PET examination of a patient, the distribution of a weakly radioactive, positron emitter-labelled substance such as, for example, a biomolecule is visualized in an organism via the radioactive disintegration of the positron emitter, using a detector.
Since biomolecules participate in the normal metabolism of the organism, accumulating in the process inter alia in tumour cells, PET can be utilized for identifying tumour cells.
One example of a radionuclide preferred for PET is gallium-68, which can be obtained using a germanium-68/gallium-68 radionuclide generator system (1, 2). With a half-life of 67.63 minutes, the isotope gallium-68 disintegrates with emission of a positron. By virtue of its physical and chemical properties, gallium-68 is highly suitable for nuclear medical examinations. Owing to its short half-life, it is particularly suitable for radiolabelling biomolecules.
Gallium-68 can be generated by radioactive disintegration from the parent nuclide germanium-68 which disintegrates with a half-life of 270.8 days.
In the generator, the germanium-68 is attached to an insoluble matrix of an inert support, where, by continuous disintegration of the germanium, gallium-68 is constantly formed and may be extracted from the generator by elution with a solvent.
The radionuclides used for labelling the radio-pharmaceutics have to meet high quality standards. In particular, the radionuclides generated have to have a high degree of purity and must be free from metallic impurities since these may, owing to competing reactions, have an adverse effect on the labelling of the radiopharmaceutics, and may reduce the technically achievable yield (3-5).
As support for the stationary phase, known germanium-68/gallium-68 generator systems use inorganic ion exchange substances, such as, for example, TiO2, SnO2, Al(OH)3. However, in a disadvantageous manner, the gallium-68 extracted therewith contains metallic impurities, such that the original eluate has to be purified prior to use in a radiopharmaceutic (4, 5).
As an alternative to inorganic ion exchange substances, generators use, as supports, organic polymers to which, with the aid of functional groups, individual molecules having a high affinity for germanium are attached. Such molecules may, for example, be pyrogallol or catechol which, via phenolic hydroxyl groups, form stable complexes with germanium (FIG. 1A) (6).
In a known germanium-68/gallium-68 generator, the support used is a resin prepared from pyrogallol and formaldehyde (4-7). During the preparation of the germanium-specific resin, pyrogallol is immobilized on the support by copolymerization with formaldehyde. However, the applicability of these materials and generator systems is limited.
Thus, with the germanium-68/gallium-68 generators mentioned above based on organic polymer, gallium-68 can be obtained only in concentrated acid solutions (3-6M). This requires reprocessing of the eluate prior to use as radiopharmaceutic.
In addition, the process for synthesizing the pyrogallol/formaldehyde resin is technically very demanding and expensive. In addition, the main component of the formaldehyde matrix is toxic, such that the preparation of an injectable radiopharmaceutic requires additional purification steps.